Two recent research developments - frequency dependent conduction block by anticonvulsants and inhibitory transmission potentiation by anticonvulsants - have led to a new understanding of how such drugs may work. These developments should now be applied to the screening and design of better antiepileptic drugs. The proposed Principal Investigator has had considerable experience with the frequency-dependent characterization of excitability blocking drugs but would now like to apply this expertise to the problem of anticonvulsant drug testing and development. High frequency nerve discharges occur in epileptic foci. Anticonvulsant drugs of several classes will be tested for their abilities to block (a) high frequency trains of action potentials in nerve and (b) high frequency antidromic bursts of action potentials generated by mammalian nerve terminals exposed to the topical convulsant agent, penicillin. Relatively simple anticonvulsant screens will thereby be developed and tested. Experimental designs proposed herein will help establish importance of frequency-dependent conduction block as a mechanism for anticonvulsant action, and elucidate structure-activity relationships regarding drug capabilities for such blocking action. Additional voltage clamp studies will serve to improve our understanding of how anticonvulsants produce such an excitability block at the sodium channel level.